Real-World Evidence (RWE) Generation for Rare Disease Drug Development and Orphan Drug Approvals

Course Outline

This course presents four topics related to generation of real-world evidence to support rare disease drug development and orphan drug approvals.

1. Natural History of Disease Studies for Rare Disease Drug Development
Emily Bratton will introduce Natural History of Disease Studies (NHODs) and outline the key differences and similarities with disease registries. Key uses for NHODs for rare disease drug development will be presented and discussed, along with rationale for NHOD, approaches in study design, execution, and methods. Methodological strategies for using natural history studies for external comparator arms (ECAs) will be described with relevant case studies and examples throughout her talk.

2. Leveraging real-world data in rare-disease study design and analysis
Daniel Rosenberg will outline the opportunities for studying rare diseases using secondary databases and federated data networks, which include studying the epidemiology and clinical prodrome/natural history of the disease, using prediction to identify patients with rare diseases earlier and applying novel methods from clinical trials to observational research for answering causal questions. For each opportunity, the methodological challenges and potential solution(s) will be discussed. Case studies will be presented for each topic.

3. Applied methods of casual inference in rare disease research
Xabier Garcia de Albeniz Martinez will:
• Review the target trial emulation framework
• Identify aspects of target trial emulation of special interest for rare disease research
• Cite case examples illustrating such aspects
• Discuss how the target trial emulation framework can help identify and tackle some of the challenges of using external comparators

4. RWE for Rare Disease Treatment – Regulatory Perspectives
Jenni Li will introduce FDA’s RWE Program and RWE Framework which direct the evaluation of RWE to support regulatory decision making. There will be discussions on RWE-related Draft Guidance’s for industry, as well as the FDA Guidance specific to rare diseases. The instructor will present key considerations for evaluating RWE in data sources, study designs, and study conducts, in the context of rare diseases to intersect with above lecturer examples. Case studies will demonstrate the quality of RWE required in support of regulatory approval for pharmacological treatments for rare diseases.